The leukotrienes are extremely potent substances which produce a wide is variety of biological effects, often in the nanomolar to picomolar concentration range. Leukotrienes are important pathological mediators in a variety of diseases. Alterations in leukotriene metabolism have been demonstrated in a number of disease states including asthma, allergic rhinitis, rheumatoid arthritis and gout, psoriasis, adult respiratory distress syndrome, inflammatory bowel disease, endotoxin shock syndrome, atherosclerosis, ischemia induced myocardial injury, and central nervous system pathology resulting from the formation of leukotrienes following stroke or subarachnoid hemorrhage.
Compounds which prevent leukotriene biosynthesis are thus useful in the treatment of disease states such as those listed above in which the leukotrienes play an important pathophysiological role.
U.S. Pat. No. 5,512,581 (Apr. 30, 1996) discloses iminoxycarboxylate derivatives which inhibit leukotriene biosynthesis. U.S. Pat. No. 5,399,699 (Mar. 21, 1995) discloses indole iminooxy derivatives which inhibit leukotriene biosynthesis.
U.S. Pat. No. 5,358,955 (Oct. 25, 1994) discloses aryl and heteroarylmethoxyphenyl compounds which inhibit leukotriene biosynthesis.
U.S. Pat. No. 4,970,215 (Nov. 13, 1990) discloses quinolylmethoxyphenyl acetic acid derivatives which inhibit leukotriene biosynthesis.
European Patent Application Number 349 062 (Jan. 3, 1990) discloses quinolylmethoxyphenyl alkanoic acid derivatives which inhibit leukotriene biosynthesis.
Prasit, et al., Bioorganic and Medicinal Chemistry Letters, 1 (11), 645 (1991) describe ((4-(4-chlorophenyl)-1-(4-(2-quinolylmethoxy)phenyl)butyl)thio)acetic acid as an orally active leukotriene biosynthesis inhibitor. Musser and Kraft, J. Med. Chem., 35 (14), 1, (1992) review quinoline containing leukotriene biosynthesis inhibitors.